- Email: [email protected]
Correlation between serum uric acid levels and residual platelet reactivity in patients undergoing PCI
Accepted Manuscript Correlation between Serum Uric Acid and Residual Platelet Reactivity in Patients undergoing PCI Giovanni Ciccarelli, Fabio Mangiacapra, Mariano Pellicano, Emanuele Barbato PII:
S0939-4753(17)30041-8
DOI:
10.1016/j.numecd.2017.02.006
Reference:
NUMECD 1703
To appear in:
Nutrition, Metabolism and Cardiovascular Diseases
Received Date: 2 February 2017 Accepted Date: 22 February 2017
Please cite this article as: Ciccarelli G, Mangiacapra F, Pellicano M, Barbato E, Correlation between Serum Uric Acid and Residual Platelet Reactivity in Patients undergoing PCI, Nutrition, Metabolism and Cardiovascular Diseases (2017), doi: 10.1016/j.numecd.2017.02.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Correlation between Serum Uric Acid and Residual Platelet Reactivity in Patients undergoing PCI
Giovanni Ciccarelli,1,2 Fabio Mangiacapra, 3 Mariano Pellicano, 1,4 Emanuele Barbato1,4
RI PT
1) Cardiovascular Research Center Aalst, OLV Hospital, Belgium; 2) Department of Cardio-Thoracic Science, University of Campania “Luigi Vanvitelli”, Naples, Italy; 3) Unit of Cardiovascular Science Department of Medicine Campus Bio-Medico University of Rome; 4) Department of Advance Biomedical Sciences, University of
Contacts: Prof. Emanuele BARBATO Moorselbaan n. 164
Tel. +32-(0)53-724447 Fax. +32-(0)53-724550
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9300 Aalst (Belgium)
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Naples Federico II, Italy;
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Word counts: 433
EP
E-mail: [email protected] or [email protected]
ACCEPTED MANUSCRIPT Uric acid has been demonstrated within atherosclerotic plaque, where it may predispose to thrombus formation by increasing platelet adhesiveness and by altering the normal platelet reactivity.[1, 2] Increased platelet reactivity has been associated with ischemic events in patients with coronary atherosclerosis.[3] In particular, recurrent ischemic events and increased risk of stent thrombosis were reported in patients undergoing
RI PT
percutaneous coronary intervention (PCI) in the presence of high residual platelet reactivity (HPR) despite treatment with dual anti-platelet therapy (DAPT) with aspirin (ASA) and P2Y12 inhibitors (e.g. Clopidogrel).
The Novara Atherosclerosis Study (NAS) group has recently demonstrated that in
SC
patients on chronic DAPT after an Acute Coronary Syndrome (ACS) or an elective PCI, the serum uric acid levels (sUA) do not influence the response to platelet function at 30-90 days
post-discharge.[4] Yet, a large heterogeneity in platelet inhibition has been demonstrated just
M AN U
at the time of the PCI[5] and whether sUA levels might have an impact on the rate of HPR is still unknown.
We investigated the association between sUA and HPR in 185 patients with stable angina undergoing elective PCI at Cardiovascular Center, OLV Clinic, Aalst, Belgium. Blood samples were collected the day before PCI for sUA, and immediately after sheath insertion for
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platelet reactivity by VerifyNow P2Y12 assay (Accumetrics, San Diego, California) that was expressed as P2Y12 reaction units (PRU). HPR was defined as PRU ≥240. Hyper-uricemia was defined as sUA > 5.9 mg/dL. Patients were uniformly loaded with 500 mg ASA and 600 mg clopidogrel at least 12 hours before PCI. Troponin T (TnT) was measured before and 24 hours
EP
after percutaneous revascularization to assess PCI related myocardial damage (PMI=defined as 10 times TnT elevation).
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Mean age of the patients was 68 ± 10 years, 72% (134/188 patients) were males. Renal failure (GFR< 60 ml/min) was present in 26% (48/188) of the patients (mean GFR 71 ± 28.3 ml/min). The incidence of HPR was 39% (73/188 patients), while hyperuricemia was detected in 56% (103/188) of the patients. Patients with elevated sUA showed a higher incidence of renal failure than patients without elevated sUA (p=0,034). No significant differences were observed for gender, smoking habits, diabetes, and age. No correlation was found between sUA and PRU (r= 0.135; p= 0.084). PMI was detected in 6% (12/185) patients, with no significant difference between patients with and without elevated sUA (p=0,312). Our findings confirm and further extend the results from the NAS group demonstrating no association between sUA and HPR in patients undergoing PCI even in the peri-procedural phase. Moreover, we found that the association of HPR and elevated sUA does not predict PMI.
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RI PT
ACCEPTED MANUSCRIPT
References
ACCEPTED MANUSCRIPT
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[1] Suarna C, Dean RT, May J, Stocker R. Human atherosclerotic plaque contains both oxidized lipids and relatively large amounts of alpha-tocopherol and ascorbate. Arteriosclerosis, thrombosis, and vascular biology. 1995;15:1616-24. [2] Ginsberg MH, Kozin F, O'Malley M, McCarty DJ. Release of platelet constituents by monosodium urate crystals. The Journal of clinical investigation. 1977;60:999-1007. [3] Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. Journal of the American College of Cardiology. 2010;56:919-33. [4] Barbieri L, Verdoia M, Pergolini P, Nardin M, Rolla R, Marino P, et al. Uric acid and highresidual platelet reactivity in patients treated with clopidogrel or ticagrelor. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2016;26:352-8. [5] Mangiacapra F, Bartunek J, Bijnens N, Peace AJ, Dierickx K, Bailleul E, et al. Periprocedural variations of platelet reactivity during elective percutaneous coronary intervention. Journal of thrombosis and haemostasis : JTH. 2012;10:2452-61.
S0939-4753(17)30041-8
DOI:
10.1016/j.numecd.2017.02.006
Reference:
NUMECD 1703
To appear in:
Nutrition, Metabolism and Cardiovascular Diseases
Received Date: 2 February 2017 Accepted Date: 22 February 2017
Please cite this article as: Ciccarelli G, Mangiacapra F, Pellicano M, Barbato E, Correlation between Serum Uric Acid and Residual Platelet Reactivity in Patients undergoing PCI, Nutrition, Metabolism and Cardiovascular Diseases (2017), doi: 10.1016/j.numecd.2017.02.006. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Correlation between Serum Uric Acid and Residual Platelet Reactivity in Patients undergoing PCI
Giovanni Ciccarelli,1,2 Fabio Mangiacapra, 3 Mariano Pellicano, 1,4 Emanuele Barbato1,4
RI PT
1) Cardiovascular Research Center Aalst, OLV Hospital, Belgium; 2) Department of Cardio-Thoracic Science, University of Campania “Luigi Vanvitelli”, Naples, Italy; 3) Unit of Cardiovascular Science Department of Medicine Campus Bio-Medico University of Rome; 4) Department of Advance Biomedical Sciences, University of
Contacts: Prof. Emanuele BARBATO Moorselbaan n. 164
Tel. +32-(0)53-724447 Fax. +32-(0)53-724550
TE D
9300 Aalst (Belgium)
M AN U
SC
Naples Federico II, Italy;
AC C
Word counts: 433
EP
E-mail: [email protected] or [email protected]
ACCEPTED MANUSCRIPT Uric acid has been demonstrated within atherosclerotic plaque, where it may predispose to thrombus formation by increasing platelet adhesiveness and by altering the normal platelet reactivity.[1, 2] Increased platelet reactivity has been associated with ischemic events in patients with coronary atherosclerosis.[3] In particular, recurrent ischemic events and increased risk of stent thrombosis were reported in patients undergoing
RI PT
percutaneous coronary intervention (PCI) in the presence of high residual platelet reactivity (HPR) despite treatment with dual anti-platelet therapy (DAPT) with aspirin (ASA) and P2Y12 inhibitors (e.g. Clopidogrel).
The Novara Atherosclerosis Study (NAS) group has recently demonstrated that in
SC
patients on chronic DAPT after an Acute Coronary Syndrome (ACS) or an elective PCI, the serum uric acid levels (sUA) do not influence the response to platelet function at 30-90 days
post-discharge.[4] Yet, a large heterogeneity in platelet inhibition has been demonstrated just
M AN U
at the time of the PCI[5] and whether sUA levels might have an impact on the rate of HPR is still unknown.
We investigated the association between sUA and HPR in 185 patients with stable angina undergoing elective PCI at Cardiovascular Center, OLV Clinic, Aalst, Belgium. Blood samples were collected the day before PCI for sUA, and immediately after sheath insertion for
TE D
platelet reactivity by VerifyNow P2Y12 assay (Accumetrics, San Diego, California) that was expressed as P2Y12 reaction units (PRU). HPR was defined as PRU ≥240. Hyper-uricemia was defined as sUA > 5.9 mg/dL. Patients were uniformly loaded with 500 mg ASA and 600 mg clopidogrel at least 12 hours before PCI. Troponin T (TnT) was measured before and 24 hours
EP
after percutaneous revascularization to assess PCI related myocardial damage (PMI=defined as 10 times TnT elevation).
AC C
Mean age of the patients was 68 ± 10 years, 72% (134/188 patients) were males. Renal failure (GFR< 60 ml/min) was present in 26% (48/188) of the patients (mean GFR 71 ± 28.3 ml/min). The incidence of HPR was 39% (73/188 patients), while hyperuricemia was detected in 56% (103/188) of the patients. Patients with elevated sUA showed a higher incidence of renal failure than patients without elevated sUA (p=0,034). No significant differences were observed for gender, smoking habits, diabetes, and age. No correlation was found between sUA and PRU (r= 0.135; p= 0.084). PMI was detected in 6% (12/185) patients, with no significant difference between patients with and without elevated sUA (p=0,312). Our findings confirm and further extend the results from the NAS group demonstrating no association between sUA and HPR in patients undergoing PCI even in the peri-procedural phase. Moreover, we found that the association of HPR and elevated sUA does not predict PMI.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
References
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
[1] Suarna C, Dean RT, May J, Stocker R. Human atherosclerotic plaque contains both oxidized lipids and relatively large amounts of alpha-tocopherol and ascorbate. Arteriosclerosis, thrombosis, and vascular biology. 1995;15:1616-24. [2] Ginsberg MH, Kozin F, O'Malley M, McCarty DJ. Release of platelet constituents by monosodium urate crystals. The Journal of clinical investigation. 1977;60:999-1007. [3] Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R, et al. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. Journal of the American College of Cardiology. 2010;56:919-33. [4] Barbieri L, Verdoia M, Pergolini P, Nardin M, Rolla R, Marino P, et al. Uric acid and highresidual platelet reactivity in patients treated with clopidogrel or ticagrelor. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2016;26:352-8. [5] Mangiacapra F, Bartunek J, Bijnens N, Peace AJ, Dierickx K, Bailleul E, et al. Periprocedural variations of platelet reactivity during elective percutaneous coronary intervention. Journal of thrombosis and haemostasis : JTH. 2012;10:2452-61.